Transcriptome-wide association study for postpartum depression implicates altered B-cell activation and insulin resistance.
Transcriptome-wide association study for postpartum depression implicates altered B-cell activation and insulin resistance.
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DOI：
10.1038/s41380-022-01525-7
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发表时间：
2022-06
影响因子：
11
通讯作者：
van den Oord, Edwin J. C. G.
中科院分区：
文献类型：
--
作者：
Guintivano, Jerry;Aberg, Karolina A.;Clark, Shaunna L.;Rubinow, David R.;Sullivan, Patrick F.;Meltzer-Brody, Samantha;van den Oord, Edwin J. C. G.
产后抑郁症（PPD）影响七分之一的妇女，并对母亲和儿童的心理健康产生负面影响。然而，这种疾病背后的确切生物学机制尚不清楚。因此，我们使用全血和去卷积细胞类型的RNA测序进行了迄今为止最大的PPD全转录组关联研究（TWAS）（482例，859例对照）。在全血中未观察到转录变化。B细胞显示出大部分转录组范围的显著结果（891个转录物代表789个基因），通路分析暗示改变的B细胞活化和胰岛素抵抗。其他数据类型的整合显示细胞类型特异性DNA甲基化位点和疾病相关eQTL（deQTL），但不是激素/神经肽（雌二醇，孕酮，催产素，BDNF），作为病例和对照之间的部分转录差异的调节因子。此外，deQTL富集了几个脑区特异性eQTL，但没有观察到与MDD风险位点的重叠。总之，我们的研究结果构成了PPD中受影响最大的途径的证据与不同生物机制的数据的融合。
Postpartum depression (PPD) affects 1 in 7 women and has negative mental health consequences for both mother and child. However, the precise biological mechanisms behind the disorder are unknown. Therefore, we performed the largest transcriptome-wide association study (TWAS) for PPD (482 cases, 859 controls) to date using RNA-sequencing in whole blood and deconvoluted cell types. No transcriptional changes were observed in whole blood. B-cells showed a majority of transcriptome-wide significant results (891 transcripts representing 789 genes) with pathway analyses implicating altered B-cell activation and insulin resistance. Integration of other data types revealed cell type-specific DNA methylation loci and disease-associated eQTLs (deQTLs), but not hormones/neuropeptides (estradiol, progesterone, oxytocin, BDNF), serve as regulators for part of the transcriptional differences between cases and controls. Further, deQTLs were enriched for several brain region-specific eQTLs, but no overlap with MDD risk loci was observed. Altogether, our results constitute a convergence of evidence for pathways most affected in PPD with data across different biological mechanisms.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
3.4
作者：
Babenko VN;Chadaeva IV;Orlov YL
通讯作者：
Orlov YL
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
3.7
作者：
Euesden J;Danese A;Lewis CM;Maughan B
通讯作者：
Maughan B
DOI：
10.1088/1742-5468/2008/10/p10008
发表时间：
2008-10-01
影响因子：
2.4
作者：
Blondel, Vincent D.;Guillaume, Jean-Loup;Lefebvre, Etienne
通讯作者：
Lefebvre, Etienne